• Archives of Pharmacal Research
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• v.22 no.5
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• pp.485-490
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• 1999

The mechanism of action of fish oil (FO), currently used in different chronic inflammatory conditions such as rheumatoid arthritis (RA), is not completely understood, although it is thought that it could alter the metabolism of endogenous autacoids. In addition, we hypothesized that the known capability of fatty acids (FA) of stabilizing serum albumin and perhaps other proteins, may be of pharmacological relevance considering that it is shared by other anti-rheumatic agents (e.g. nonsteroidal antiinflammatory drugs). Thus, we studied the effect of oral administration of FO and corn oil (CO), a vegetable oil with a different composition, on the stability of rat serum proteins, evaluated buy a classical in vitro method based on heat-induced protein denaturation. FO, and, to a lower extent, CO inhibited heat-induced denaturation of rat serum (RS): based on the inhibitory activity (EC50) of the major fatty acids against heat-induced denaturation of RS in vitro, it was possible to speculate the in vivo effects of palmitic acid (C16:0) and eicosapentaenoic acid (EPA, C20:5, n-3) may be more relevant than that of linolenic acid (C18:2). To better investigate this phenomenon, we extracted albumin from the serum of animals treated or not with FO with a one-step affinity chromatography technique, obtaining high purity rat serum albumin preparations (RSA-CTRL and RSA-FO), as judged by SDS-PAGE with Coomassie blue staining. When these RSA preparations were heated at $70^{\circ}C$ for 30 min, it was noted that RSA-FO was much more stable than RSA-CTRL, presumably due to higher number of long chain fatty acids (FA) such as palmitic acid or EPA. In conclusion, we provided evidences that oral administration of FO in the rat stabilizes serum albumin, due to an increase in the number of protein bound long chain fatty acids (e.g. palitic acid and EPA). We speculate that the stabilization of serum albumin and perhaps other proteins could prevent changes of antigenicity due to protein denaturation and glycosylation, which may trigger pathological autoimmune responses, suggesting that this action may be involved in the mode of action of FO in RA and other chronic inflammatory diseases.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.383-389
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• 2021

Obesity is associated with impaired intestinal epithelial barrier function, which contribute to host systemic inflammation and metabolic dysfunction. Korean traditional foods, fiber-rich bean products, have been various biological activities in anti-inflammatory responses, but has not reported the large intestinal health. In this study, we investigated the intestinal health promoting effect of cooked soybeans (CSB) on high fat diet (HFD)-induced obesity model. SD rat were fed either a HFD or HFD supplemented with 10.6% CSB (HFD+CSB) for animal experimental period. CSB treatment significantly decreased the HFD-induced weights of body and fat. Also, CSB treatment improved HFD-reduced tight junction components (ZO-1, Claudin-1, and Occludin-1) mRNA expression in large intestine tissue. Additionally, histopathological evaluation showed that CSB treatment attenuated the HFD-increased inflammatory cells infiltration and epithelial damages in large intestine tissue. At the genus level, effects of CSB supplement not yet clear, while dietary effects showed differential abundance of several genera including Lactobacillus, Duncaniella, and Alloprevotella. NMDS analysis showed significant microbial shifts by HFD, while CSB did not shift gut microbiota. CSB increased the abundance of the genera Anaerotignum, Enterococcus, Clostridium sensu stricto, and Escherichia/Shigella by linear discriminant analysis effect size analysis, while reduced the abundance of Longicatena and Ligilactobacillus. These findings indicate that CSB supplement improves HFD-deteriorated large intestinal health by the amelioration of tight junction component, while CSB did not shift gut microbiotas.

• Journal of Food Hygiene and Safety
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• v.38 no.6
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• pp.442-448
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• 2023

This study aimed to prepare kombucha, a fermented tea beverage, containing Dendropanax morbiferus (DM) leaves and roots, and analyze its antioxidant and intracellular activities. We compared the pH change, total acidity, radical scavenging activity, and oxygen radical absorbance capacity (ORAC) of kombucha fermented with black tea alone and that with added DM leaves or roots during fermentation. Using RAW 264.7, we evaluated the effects of kombucha containing different DM parts on nitric oxide (NO) production and inflammation-related cytokine content in cells. Kombucha containing ethanol extracts of DM leaves (BTK-E-DML) and roots (BTK-E-DMR) showed higher radical scavenging activity and ORAC 3 d after fermentation than that prepared from black tea alone (BTK-Ori). In an in vitro experiment using RAW 264.7, samples were treated with 8 mg/mL kombucha considering cytotoxicity; the lipopolysaccharide (LPS)-induced NO content significantly reduced after BTK-E-DML and BTK-EDMR treatments compared with that after BTK-Ori treatment. Additionally, the levels of interleukin-6 and tumor necrosis factor-alpha, which were LPS-stimulated inflammatory cytokines, significantly decreased in cells treated with BTK-E-DML and BTK-E-DMR 15 d after fermentation compared with those treated with BTK-Ori. In conclusion, these results demonstrate that kombucha fermented with the leaves and roots of DM increases antioxidant activity and can significantly regulate inflammatory responses at the cellular level.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Journal of Life Science
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• v.30 no.11
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• pp.999-1006
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• 2020

The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH₂) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.

• Journal of Life Science
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• v.17 no.1 s.81
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• pp.12-17
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• 2007

Curcumin is a natural phenolic yellow curry spice, derived from the tumeric, which has been used for the treatment of diseases associated with oxidative stress and inflammation. Curcumin is known to have both anti-oxidative and anti-inflammatory properties. These properties can be beneficial to protect the brain from the neurodegenerative diseases. We now report the neuroprotective effects of curcumin pretreatment in primary hippocampal neurons to glutamate-induced excitotoxicity. Pretreatment of embryonic mouse hippocampal cell cultures with low does of curcumin protected neurons against glutamate-induced death, however, this neuroprotection was not correlated with the modulation of oxidative stress. Interestingly, high dose of curcumin showed the cytotoxicity in primary cultured hippocampal neurons. Immunoblot analyses showed that levels of stress response. protein HSP70 were significantly elevated in neurons exposed to low dose of curcumin, whereas levels of cleaved PARP were increased in neurons exposed to high dose of curcumin. These findings show that curcumin can modulate neuronal responses to glutamate, and suggest possible use of curcumin and related compounds in the prevention and/or treatment of neurodegenerative disorders.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.625-634
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• 2011

Green tea seed coat (GTSC) was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether (PE), ethyl acetate (EtOAC) and butanol (BuOH). The EtOAC fraction showed the highest level in total phenol contents and the lowest level in nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophage cell. Thus, this study was carried out to investigate the anti-inflammatory and its mechanisms of GTSC EtOAC fraction in LPS-stimulated RAW264.7 macrophage cell. GTSC EtOAC fraction contained EGC ($1146.48{\pm}11.01\;{\mu}g/g$), tannic acid ($966.99{\pm}32.24\;{\mu}g/g$), EC ($70.88{\pm}4.39\;{\mu}g/g$), gallic acid ($947.61{\pm}1.03\;{\mu}g/g$), caffeic acid ($37.69{\pm}1.46\;{\mu}g/g$), ECG ($35.46{\pm}3.19\;{\mu}g/g$), and EGCG ($15.53{\pm}0.09\;{\mu}g/g$) when analyzed by HPLC. NO production was significantly (p<0.05) suppressed in a dose-dependent manner with an $IC_{50}$ of $80.11\;{\mu}g$/mL. Also prostaglandin $E_2$ level was also inhibited in a dose-dependent manner. Moreover, iNOS protein expression was suppressed in dose-dependent manner but COX-2 gene expression was not affected. Total antioxidant capacity and glutathione (GSH) levels were enhanced more than the LPS-control. Expressions of antioxidative enzymes including catalase, GSH-reductase and Mn-SOD were elevated compared to LPS-control. Nuclear p65 level was decreased in the GTSC EtOAC fraction in a dose-dependent manner. These results indicate that GTSC EtOAC fraction inhibit oxidative stress and inflammatory responses through elevated GSH levels, antioxidative enzymes expressions and suppression of iNOS expression via NF-${\kappa}B$ down-regulation.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

• Journal of the Korean Applied Science and Technology
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• v.37 no.3
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• pp.448-462
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• 2020

Dietary nutrition is a critical lifestyle factor that can reduce the risk of future cognitive impairments caused by dementia. Accumulating evidence suggests that dietary supplementation with Sulforaphane may help the prevention of cognitive impairments and dementia. Thus, Sulforaphane-enriched broccoli extract would hold promise to improve cognitive impairments of dementia patients. Here, we have used broccoli extracts, prepared from broccoli cultivated in Magma Seawater, to test if the broccoli extracts can be dietary supplement to improve cognitive impairments. Magma Seawater originated from Jeju Island, Korea is unique in terms of containing high concentrations of usable minerals (Zinc, Vanadium and Germanium etc.). Broccoli, grown in Magma Seawater, would contain Sulforaphane and the extra amount of usable minerals. The chemical compositions of the broccoli extracts were analyzed using LC-Q-orbitrap to detect Sulforaphane and Glucoraphanin. Analysis method based on HPLC was developed for measurement of sulforaphane levels in the broccoli extracts. We have tested if the broccoli extracts have anti-apoptotic and anti-inflammatory effects on neuron-like SH-SY5Y cells. In addition, we examined if the broccoli extracts are able to upregulate expression of synaptic plasticity-associated proteins (BDNF and phospho-CREB) and to inhibit acetylcholine esterase (AchE) activity. We have shown that the broccoli extracts inhibited the apoptotic pathway and inflammatory responses. Finally, we present evidence showing that AchE activity was inhibited by the broccoli extracts, but expression of BDNF and phospho-CREB was upregulated. Taken together, these findings suggest that the broccoli extracts from Magma Seawater-grown broccoli would be a good source of dietary nutrition to improve cognitive impairments in the future.

• Journal of Animal Science and Technology
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• v.55 no.4
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• pp.281-288
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• 2013

This experiment was conducted to determine the effects of extracts from fruit by-products on the blood characteristics, antioxidant activities, and immune response to Escherichia coli lipopolysaccharide (LPS) in growing pigs. A total of 96 pigs [(Landrace ${\times}$ Yorkshire) ${\times}$ Duroc] with an initial BW of $27.94{\pm}0.92kg$ were used in a 6-week feeding trial. The pigs were randomly placed into one of four treatment groups with six replications (four pigs per replication) per treatment according to their initial BW. Treatments were: 1) CON (basal diet), 2) PRO (CON + 0.5% procyanidin), 3) HES (CON + 0.5% hesperetin), 4) TAN (CON + 0.5% tannin). At the end of the sixth week, five pigs (total 20 pigs, $BW=27.94{\pm}0.92kg$) were selected from each treatment and injected with LPS ($100{\mu}g/kg$ of BW). Blood samples were collected 3 h after LPS injection to assess anti-oxidative and inflammatory responses. After the LPS challenge, the concentration of serum cholesterol decreased with fruit by-product treatment compared with CON (p<0.05). The administration of TAN increased the concentration of blood total protein compared with the CON group 3 h after LPS challenge (p<0.05). The albumin concentration was also higher with PRO treatment compared to HES treatment (p<0.05). The concentration of IgM was increased by fruit by-product supplementation at 0 and 3 h (p<0.05). In addition, IgG concentration was higher in PRO, HES, and TAN treatments compared to CON treatment at 0 h, and IgG concentrations were also higher in the HES group compared to the CON group at 3 h (p<0.05). The concentration of IgA also increased with fruit by-product treatments at 3 h (p<0.05). In conclusion, dietary supplementation with fruit by-products may moderate the immune response after a LPS challenge in growing pigs.